title: A novel protein complex promoting formation of functional alpha- and gamma-tubulin.
abstract: We describe the identification of GIM1/YKE2, GIM2/PAC10, GIM3, GIM4 and GIM5 in a screen for mutants that are synthetically lethal with tub4-1, encoding a mutated yeast gamma-tubulin. The cytoplasmic Gim proteins encoded by these GIM genes are present in common complexes as judged by co-immunoprecipitation and gel filtration experiments. The disruption of any of these genes results in similar phenotypes: the gim null mutants are synthetically lethal with tub4-1 and super-sensitive towards the microtubule-depolymerizing drug benomyl. All except Deltagim4 are cold-sensitive and their microtubules disassemble at 14 degrees C. The Gim proteins have one function related to alpha-tubulin and another to Tub4p, supported by the finding that the benomyl super-sensitivity is caused by a reduced level of alpha-tubulin while the synthetic lethality with tub4-1 is not. In addition, GIM1/YKE2 genetically interacts with two distinct classes of genes, one of which is involved in tubulin folding and the other in microtubule nucleation. We show that the Gim proteins are important for Tub4p function and bind to overproduced Tub4p. The mammalian homologues of GIM1/YKE2 and GIM2/PAC10 rescue the synthetically lethal phenotype with tub4-1 as well as the cold-sensitivity and benomyl super-sensitivity of the yeast deletion mutants. We suggest that the Gim proteins form a protein complex that promotes formation of functional alpha- and gamma-tubulin.
authors.affiliation: Max-Planck Institut für Biochemie, Martinsried, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Geissler
authors.forename: K
authors.initials: K
authors.lastname: Siegers
authors.forename: E
authors.initials: E
authors.lastname: Schiebel
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors; D000818:Animals; D001542:Benomyl / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D005800:Genes, Fungal / Q000187:drug effects; D005804:Genes, Lethal; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008870:Microtubules / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009997:Osmotic Pressure / Q000187:drug effects; D010802:Phylogeny; D011485:Protein Binding / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014170:Transformation, Genetic; D014404:Tubulin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C100764:TUB4 protein, S cerevisiae; D013844:Thiazoles; D053778:Thiazolidines; D014404:Tubulin; C108825:VBP1 protein, human; C484640:Vbp1 protein, mouse; C091622:YKE2 protein, S cerevisiae; C072003:Pfdn6 protein, mouse; C037067:latrunculin A; D001542:Benomyl